In sub-Saharan Africa, 55% of the HIV-1 positive adults are women of childbearing age. The rates of pregnancy and breastfeeding in these women are high and little impaired by HIV infection1. In these societies, children are not fully weaned until 18 to 24 months of age. In Zambia, the fertility rate is 5.7 and the average life expectancy of women is 40 years2. Thus, a significant portion of a woman's life is spent lactating. Of note, lactation results in low levels of estrogen. Estrogen and other sex steroids have long been recognized as negative regulators of thymopoiesis. For example, castration of male or female rats increases thymic size, CD4 counts and the number of peripheral blood naive T cells. In accord with these experimental observations, in our cohort of HIV infected breastfeeding Zambian women, those who were randomized to early weaning at 4 months had significantly lower absolute numbers of CD4 cells (323 vs. 427, p=0.02) and lower percentages of CD4 T cells (25.9 vs. 33.3, p=0.002) at a year post-partum compared to those who continued to breast feed. These preliminary results suggest that lactation increases maternal CD4 cell counts in HIV infected women. We hypothesize that the hypoestrogenemia associated with lactation increases thymic output and is responsible for this difference. The objective of the proposed research is to test this hypothesis by analyzing the effects of lactation on measures of thymic output and to determine how this influences plasma viremia. The specific aims are: 1) To determine if increased levels of CD4+ T cells observed in associated with prolonged lactation are due to enhanced thymic output, or to T cell proliferation. Measurements of T cell receptor recombination excision circles (TREC) will be employed as a parameter of thymopoiesis. Flow cytometry will be used to quantify lymphocyte subsets and T cell turnover and cell activation. 2) To determine whether the hypoestrogenemia associated with lactation correlates with enhanced T cell proliferation or thymopoiesis. 3) To determine if prolonged breastfeeding influences levels of maternal plasma viremia. Changes in HIV plasma RNA levels over 12 months of breastfeeding will be compared to baseline levels as well as parameters of T cell turnover and thymopoiesis.